11-116763231-G-T

Variant names:

• chr11-116763231-G-T
• rs10488698
• NM_032725.4:c.358C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032725.4(BUD13):​c.358C>A​(p.Arg120Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R120H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BUD13 NM_032725.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 0 publications found

Genes affected

BUD13 (HGNC:28199): (BUD13 homolog) Enables RNA binding activity. Involved in mRNA splicing, via spliceosome. Located in nucleoplasm. Part of U2-type precatalytic spliceosome. [provided by Alliance of Genome Resources, Apr 2022]

BUD13 Gene-Disease associations (from GenCC):

• progeroid syndrome

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000308823 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07962951).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BUD13	NM_032725.4	c.358C>A	p.Arg120Ser	missense_variant	Exon 4 of 10	ENST00000260210.5	NP_116114.1
BUD13	NM_001159736.2	c.358C>A	p.Arg120Ser	missense_variant	Exon 4 of 10		NP_001153208.1
BUD13	XM_011543035.3	c.259C>A	p.Arg87Ser	missense_variant	Exon 4 of 10		XP_011541337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BUD13	ENST00000260210.5	c.358C>A	p.Arg120Ser	missense_variant	Exon 4 of 10	1	NM_032725.4	ENSP00000260210.3
BUD13	ENST00000375445.7	c.358C>A	p.Arg120Ser	missense_variant	Exon 4 of 10	1		ENSP00000364594.3
ENSG00000308823	ENST00000836679.1	n.434-2019G>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	13
DANN	Benign	0.89
DEOGEN2	Benign	0.0	.;T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.080	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.5	M;M
PhyloP100		1.0
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.058
Sift	Benign	0.40	T;T
Sift4G	Benign	0.13	T;T
Vest4		0.23
ClinPred		0.19	T
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.090
gMVP		0.096
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10488698; hg19: chr11-116633947;